Evidence map›Paper›PMID 34880103›Full record

ArticleLife science alliance2022

Nonsense-mediated mRNA decay uses complementary mechanisms to suppress mRNA and protein accumulation.

Dylan B Udy, Robert K Bradley

Open access · goldAbstract read
In one paragraph

Article in Life science alliance, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.3field-weighted citation impact, top 20% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Five novelFrontiers in genetics · 2025
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Hemizygous nonsense variant in the moesin geneFrontiers in immunology · 2022
    Article
  14. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 2 institutions in 1 country.

Dylan B UdyComputational Biology Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.ORCID 0000-0003-4440-0762
Robert K BradleyComputational Biology Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA rbradley@fredhutch.org.ORCID 0000-0002-8046-1063
Fred Hutch Cancer Center · USUniversity of Washington · US

Funding

Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Marian Esvelt · 1985 to 2026
$296.4M
TRAINING IN MOLECULAR AND CELLULAR BIOLOGYT32GM007270 · NIGMS · UNIVERSITY OF WASHINGTON · PI RAIBLE, DAVID W · 1985 to 2020
$21.0M
Genetic and molecular basis for SRSF2 mutations in myelodysplasiaR01HL128239 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Omar Abdel-Wahab, Robert K Bradley · 2015 to 2026
$8.0M
Functional and molecular consequences of SF3B1 mutations in human hematopoietic stem cellsR01HL151651 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Robert K Bradley, Sergei Doulatov · 2020 to 2026
$4.0M
Interrogating the minor spliceosome to understand and treat leukemiaR01CA251138 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI ABDEL-WAHAB, OMAR, BRADLEY, ROBERT K · 2020 to 2024
$3.3M
U2AF1 mutations in myelodysplastic syndromes: from mechanism to therapyR01DK103854 · NIDDK · FRED HUTCHINSON CANCER RESEARCH CENTER · PI BRADLEY, ROBERT K · 2016 to 2019
$1.5M
NCI NIH HHS P30 CA015704NCI NIH HHS R01 CA251138NHLBI NIH HHS R01 HL128239NHLBI NIH HHS R01 HL151651NIDDK NIH HHS R01 DK103854NIGMS NIH HHS T32 GM007270
6 · The paper itself

Abstract

Nonsense-mediated mRNA decay (NMD) is an essential, highly conserved quality control pathway that detects and degrades mRNAs containing premature termination codons. Although the essentiality of NMD is frequently ascribed to its prevention of truncated protein accumulation, the extent to which NMD actually suppresses proteins encoded by NMD-sensitive transcripts is less well-understood than NMD-mediated suppression of mRNA. Here, we describe a reporter system that permits accurate quantification of both mRNA and protein levels via stable integration of paired reporters encoding NMD-sensitive and NMD-insensitive transcripts into the AAVS1 safe harbor loci in human cells. We use this system to demonstrate that NMD suppresses proteins encoded by NMD-sensitive transcripts by up to eightfold more than the mRNA itself. Our data indicate that NMD limits the accumulation of proteins encoded by NMD substrates by mechanisms beyond mRNA degradation, such that even when NMD-sensitive mRNAs escape destruction, their encoded proteins are still effectively suppressed.

Indexed as

Gene Expression RegulationNonsense Mediated mRNA DecayGene ExpressionGene OrderGenes, ReporterHumansPlasmidsRNA-Binding ProteinsRNA InterferenceRNA, MessengerTransfectionRNA-Binding ProteinsRNA, Messenger

Identifiers

PMID34880103
PMCPMC8711849
OpenAlexW4200536482

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.